In pharmacotherapy, almost all of the macromolecular drugs and many small molecules drugs cannot enter the brain and central nervous system due to the existence of the blood brain barrier (BBB). Whether the drug can be delivered to penetrating the blood brain barrier and still reaching an effective therapeutic concentration is critical for the treatment of glioma. After traditional administration of chemical treatment drugs, the drugs cannot directly and effectively act on lesions due to the physiological response of the subject itself. The blood brain barrier is a key barrier for intracranial drug delivery for treating brain diseases.
The so-called blood brain barrier is a selective permeable “Neurovascular Unit” (NVU) composed of a specific physical structure, various enzymes and transporters. Its anatomical structures of specific barrier is selected from the group consisting of: endothelial cell layer closely jointed by brain capillary, continuous basement membrane layer outside of the endothelial cells, pericytes in the outer wall of the cerebral capillaries, and astrocyte end-feet, which constitute a barrier between the blood and brain tissue that has important significance to maintain the homeostasis of brain tissue and the normal physiological function of intracranial central nervous system (CNS). In brain diseases, brain gliomas (gliomas) account for about 46 percent of intracranial tumors and 1 to 3 percent of all malignant tumors of the whole body. With extremely high mortality and recurrence rates, gliomas seriously threaten human health. In clinical treatment of malignant glioma, the priority is still given to surgery supplemented with radiotherapy and chemotherapy. Because of the presence of the blood brain barrier, 98% of small molecular and almost all of macromolecular drugs cannot reach to the intracranial tumor tissue. Therefore, how to penetrate the Blood Brain Barrier (BBB) is the key to realize the new strategy of nerve injury repair and antitumor combined administration.
GM1 (Ganglioside M1) is one of the most important gangliosides, which is the main type of mammalian gangliosides and has the highest content in CNS gray matter. Endogenous GM1 is the main component of nerve cell membrane and plays an important role in nerve cell differentiation, regeneration and signal transmission, and most of the neurodegeneration and injuries are associated with the absence of GM1. Studies have shown that the supplementation of exogenous GM1 has beneficial effects on promoting nerve reparation and regeneration to nerve injury caused by ischemia, hypoxia, drug toxicity and trauma. Its effectiveness, high safety and high tolerance dose have been widely proven in the clinical treatment of cerebral apoplexy, brain trauma, Parkinson and other neurodegenerative diseases. GM1 is the only exogenous ganglioside that can penetrate the blood brain barrier and has been proved to play an important physiological role in the differentiation, growth and regeneration of nerve cells. However, currently no relevant literature has shown that drug-loaded GM1 micelle is used for administration of intracranial drug by penetrating blood-brain barrier.
Therefore, with its characteristics of BBB penetrating, nerve injury repairing and high security, GM1 will be a carrier material of a nano drug delivery system for treating malignant tumors and penetrating other intracranial blood-brain barriers.